Although there have been a number of reports of cases of transient HIV infection in both adults and babies born to HIV+ mothers, a recent re-evaluation of many of the stored PBMC samples from infant cases indicated that there was little solid evidence that transient infection ever occurred. We now have the best evidence to date that transient infection does occur in adults, showing by two independent tests (serum antibodies [Ab] to conformational epitopes of gp160 and direct presence of virus in PBMC) that approximately 20% of EIA-negative, high-risk individuals studied over a 4-year period become transiently infected at least one time. The Ab and virus are detectable for 1-3 months, and then both disappear. We showed by paternity typing that PBMC samples taken at the time of transient positivity, and later when negative, were from the same invividual. We also showed that the viruses present in PBMCs of several transiently infected subjects were not laboratory contaminants. Our current hypothesis is that transient HIV infection does occur at significant frequencies in high-risk adults, and is probably due to the presence of certain types of immune responses induced immediately after infection, as well as certain host genes which negatively influence either virus infection or spread. Four Specific Aims are proposed to address this hypothesis: 1) to further substantiate transient HIV infection and delineate its epidemiological frequencies in high-risk adults; 2) to quantitate HIV neutralizing and ADCC activities of the antibody responses present during transient infection; 3) to assess the T-cell responses in transiently infected individuals at the time of virus positivity and at later time points when virus cannot be detected; and 4) to characterize the HIV strains present during the period of transient infection, and to assess the host genotype for genes known to influence HIV. It obviously would be important to understand why some individuals can spontaneously eliminate HIV, while others cannot, and if it is immune-mediated, then this would be important fundamental information for developing a protective vaccine.